Chronic Fatigue Syndrome and the CDC: A Long, Tangled Tale

23 November 2011

by David Tuller

Note: This account draws from interviews, a close reading of a fraction of the 4608 studies that pop up (as of today; yesterday it was 4606) on a PubMed search for “chronic fatigue syndrome,” and a review of many pages of government documents–in particular the minutes and testimony from meetings of the Chronic Fatigue Syndrome Advisory Committee to the U.S. Department of Health and Human Services, one of many such panels established to provide guidance to federal health officials. Not much here will be a surprise to anyone who has read the better ME/CFS blogs, or Hillary Johnson’s authoritative and prodigiously researched 1996 account, Osler’s Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic. I want to thank Professor Racaniello for letting me invade his space to post this very long story.

In the early 1990s, Mary Schweitzer, a history professor at Villanova University near Philadelphia, suffered through successive bouts of sickness—mononucleosis associated with Epstein-Barr virus, a stomach parasite, repeated episodes of bronchitis. One day, while reviewing student exams in her office, she slumped over and blacked out. Not long after, she received a diagnosis of chronic fatigue syndrome.

In written testimony to a federal advisory committee a few years ago, Dr. Schweitzer described how disabled she eventually became: “On a bad day, I would never get up at all, or would lie in bed curled up under the covers…I experienced pain behind my eyes and in the back of my neck. It felt as if somebody had hit me in the back of the head with a baseball bat, and someone else was trying to unscrew my eyeballs with a pair of pliers.”

Over the years, Dr. Schweitzer has tested positive for multiple viruses. She experiences severe lapses in memory, concentration and other cognitive skills. She suffers from “neurally mediated hypotension,” a form of low blood pressure arising from nerve dysfunction, which causes nausea, loss of balance, and fainting. Her muscle and joint pain can be intense, and she frequently requires a wheelchair. Her white blood cell counts have been way off; her immune system is often out of whack. She left her position at Villanova because of disability and has been unable to work most of the years since.

Like others with chronic fatigue syndrome, Dr. Schweitzer is used to having her illness ignored, mocked or treated as a manifestation of trauma, depression or hypochondria—not only by doctors, colleagues and strangers but by friends, family members and federal researchers, too. So when the U.S. Centers for Disease Control and Prevention reported last year that people with chronic fatigue syndrome are more likely to suffer from “maladaptive personality features”—in particular from “higher scores on neuroticism” and higher rates of “paranoid, schizoid, avoidant, obsessive-compulsive and depressive personality disorders”—Dr. Schweitzer dismissed the research as “incredibly stupid” but “not surprising.” In another recent study, the CDC had reported—also incredibly stupidly, from Dr. Schweitzer’s perspective–that childhood trauma, such as sexual or emotional abuse, was a “an important risk factor” for the illness.

For Dr. Schweitzer, other patients and advocates, and much if not all of the non-CDC research community involved with the illness, those two studies symbolize much of what has gone wrong with the agency’s research program on chronic fatigue syndrome. As the country’s leading public health organization, the CDC has enjoyed remarkable success in the fight against many diseases. But its history with chronic fatigue syndrome, commonly called CFS, is a matter of bitter–and ongoing—dispute.

“We’re talking about a million people who are really, really sick with something,” said Dr. Schweitzer, 61, in one of a series of recent conversations. “And we have been mistreated for years by people who are convinced that it’s just personality disorders or stress or some behavior that we can change and miraculously be well. None of us want to be sick or are doing this to ourselves.”

The CDC’s mandate is to investigate threats to the health and safety of the population; develop ways to prevent, disable or mitigate those threats; and disseminate key information to the public, policy-makers, health care providers and other audiences. Given those varied responsibilities, the CDC’s pronouncements about any topic—in this case, chronic fatigue syndrome–exert an enormous impact on policy, clinical care, insurance reimbursement and public attitudes. Advocates say that when the agency reports that people with CFS suffer from paranoid personality disorder, the public remembers the association, as do other scientists, government officials, health care providers, and insurance adjusters.

In fact, since the CDC first investigated an outbreak of a non-resolving, flu-like illness in the Lake Tahoe area in the mid-1980s, the agency’s CFS program has been marked by financial scandal, an epidemiologic strategy rejected as fatally flawed by the top researchers in the field, and the kind of toxic relationship with much of the patient community that can undermine the trust and cooperation needed for effective policy-making and public health strategies. On a more substantive level, over the past quarter-century, the CDC’s research program has yielded little or no actionable information about causes, biomarkers, diagnostic tests, or pharmaceutical treatments. Nor has the agency done much to track long-term outcomes–such as cancer rates, heart attacks and suicides–among people with the illness.

The reason for those failures, critics charge, is that the CDC has spent years looking in the wrong places. Starting with its 1988 report on the illness, they say, the agency has downplayed or dismissed abundant evidence that CFS is an organic disease, or cluster of diseases, characterized by severe immune-system and neurological dysfunctions as well as the frequent presence of multiple viral infections. Instead, say the critics, the agency has focused major resources on investigating proposed psychiatric and trauma-related factors and associations–the personality disorder and trauma studies were published, respectively, in the journals Psychotherapy and Psychosomatics and Archives of General Psychiatry–even though stress and trauma make people more vulnerable to any number of health conditions.

Moreover, they charge, the CDC’s website on the illness has long been a font of misinformation and has been routinely used by insurance companies to deny legitimate claims for tests ordered by doctors. (After years of complaints from patients and doctors, a paragraph that dismissed the usefulness of many tests, including those for various infectious agents, was finally changed this month.) Critics also note that the CDC website does not incorporate much clinical expertise from doctors who have treated patients for years, but it does highlight a behavioral form of treatment—a gradual increase in exercise, known as “graded exercise therapy”–that is widely discredited in the CFS community. Patient surveys and anecdotal testimony, as well as an increasingly robust body of research, suggest that the therapy might cause severe relapses in CFS patients by encouraging over-exertion.

“The CDC has never taken chronic fatigue syndrome seriously,” said San Francisco writer and former psychotherapist Michael Allen, who suffered a severe flu in the early 1990s and has never recovered his health. “They pay lip service to it being a serious physical illness, but in their hearts they think it’s just a form of mental illness.”

Much of the anger for the CDC’s perceived failings over the years has targeted Dr. William Reeves, an epidemiologist and architect of the CFS research program from 1989 until his abrupt move last year to another division of the agency. With his gruff and sometimes dismissive manner, Dr. Reeves was never popular with the patient community, which came to view him as hostile to the search for viral or other organic causes of the illness; many non-CDC researchers echoed that complaint. When it emerged in the late 1990s that the agency had been diverting funds designated for CFS to other programs and then lying to Congress about it, Dr. Reeves—who was in charge of the program while the financial irregularities were taking place–sought and received whistle-blower protection.

Dr. Reeves also enraged the patient community by his refusal to consider changing the much-hated name of the disease—a name endorsed by the CDC in its 1988 paper and aggressively promoted in a public awareness campaign the agency launched in the mid-2000s. Patients say the name, like the term ‘yuppie flu,’ reinforces stereotypes that they are a bunch of self-entitled whiners and malingerers and that the illness itself is a form of hysteria, the latter-day version of the Victorian malady known as “neurasthenia.” That’s why many doctors, researchers and patients have long promoted a less-stigmatizing clinical name for the illness that predated the selection of chronic fatigue syndrome: “myalgic encephalomyelitis,” or ME, which means “muscle pain with inflammation of the central nervous system.”

It is not possible to exaggerate how much patients despise the name and believe it has hindered public understanding—and how much they fault the CDC and Dr. Reeves for championing it. “If they’d hired a focus group to come up with a name that screams ‘silly’ and ‘meaningless,’ they couldn’t have done a better job than ‘chronic fatigue syndrome,’” said Dr. Schweitzer.

In an interview with The New York Times earlier this year, bestselling author Laura Hillenbrand (Seabiscuit, Unbroken), who has lived with CFS for decades, called the name of the illness “condescending” and “so grossly misleading.” She added: “The average person who has this disease, before they got it, we were not lazy people; it’s very typical that people were Type A and hard, hard workers… Fatigue is what we experience, but it is what a match is to an atomic bomb. This disease leaves people bedridden. I’ve gone through phases where I couldn’t roll over in bed. I couldn’t speak. To have it called ‘fatigue’ is a gross misnomer.”

After Dr. Reeves unveiled a revised epidemiologic method for identifying people with CFS, the CDC estimated in 2007 that there were 4 million people in the U.S. with the illness—a remarkable ten-fold increase over the previous CDC estimate in 2003. Other experts dismissed this dramatic rise as an artifact of the agency’s poor epidemiology. Subsequent research reported that the new CDC approach misclassified people with primary depression as having chronic fatigue syndrome, when they did not; that kind of misclassification could easily lead to increased prevalence rates as well as false and possibly harmful research results.

In the late 2000s, leading patient, advocacy and scientific organizations engaged in an increasingly public revolt against Dr. Reeves’ leadership. In January of 2010, the CDC abruptly appointed him as senior advisor for mental health surveillance in another part of the agency. Dr. Elizabeth Unger, an expert on human papillomavirus who had worked with Dr. Reeves for years, was named to replace him—first temporarily, then permanently–as chief of the Chronic Viral Diseases Branch, which currently houses the chronic fatigue syndrome program.

Now, almost two years after Dr. Reeves’ departure, advocates and researchers say they have seen a shift in tone—some believe it is genuine, others not–but so far little change in substance. (Requests to interview both Dr. Reeves and Dr. Unger, conveyed through the CDC media office, were declined; however, with a press officer acting as intermediary, Dr. Unger responded to questions via e-mail.)

“I’m committed to continuing an aggressive program to address the needs of CFS patients and families for quality medical care and to move CFS into the mainstream of public health,” wrote Dr. Unger. She added that the agency is developing new materials about CFS for medical and health care professionals, and has contracted for studies that will help clarify questions about how to identify the illness.

Dr. Unger has made a point of meeting with patient, advocacy and scientific organizations. In contrast to her predecessor, she has impressed some advocates and researchers with her willingness to listen to their concerns and seek out joint initiatives. But reflecting a widespread view, one activist (who preferred to remain anonymous) said that “overall, I do not feel much has changed under Dr. Unger…I do look forward to changing my mind, though, if appropriate actions are taken.”

Another person with a long history of involvement in the CFS issue offered a similar assessment, noting that Dr. Unger needs to do much more, and do it more quickly, to demonstrate that she’s pursuing a different approach. “I think she has got a window of opportunity, but the patient community is only going to give her so long,” said this advocate. “She can throw off the Reeves mantle and make a break with the past, or she can maintain the past. But there’s not a middle ground here, and she’s got to make a decision.”

Kim McCleary, president and CEO of the CFIDS Association of America, the oldest organization on the illness, said she believes Dr. Unger “is trying to restore some credibility to the CDC’s program.” But, added McCleary, whose organization worked closely with Dr. Reeves for years but ultimately opposed his leadership, “she’s not going to move quickly, she’s not going to do anything bold, she’s going to move pretty methodically along a linear path.”

Although Dr. Reeves’ departure received little public notice, it was a watershed event for patients and advocates, many of whom blame the agency for the prolonged lack of significant progress in CFS research. (They also blame years of inadequate funding from the National Institutes of Health, but that’s another long story; it is worth noting, however, that the NIH online database of spending by disease category indicates only $4 to $6 million allocated annually for CFS in recent years, a small amount compared to other illnesses associated with similar levels of morbidity. While the roles of the CDC and NIH can overlap significantly, the NIH generally focuses more on basic research into disease processes than on epidemiology and the development of public health strategies and interventions.)

The personnel shift at the CDC also occurred during a volatile period in the scientific domain. In October 2009, the journal Science published a headline-grabbing study that linked CFS to XMRV, a poorly understood mouse leukemia retrovirus. The finding thrilled the patient community because it appeared to offer a plausible explanation for the disease and to suggest treatment possibilities. Although a second study found links between CFS and a group of mouse leukemia retroviruses related to XMRV, other research has failed to support the proposed association. The Science report was partially retracted earlier this year, and most researchers now believe the initial findings were an artifact of laboratory contamination. Results expected early next year from a large NIH-sponsored study should settle the XMRV issue, although not the issue of whether another retrovirus might eventually be linked to cases of CFS.

(In the meantime, in a bizarre and unsettling turn of events, the senior author of the original XMRV paper, Dr. Judy Mikovits, is engaged in a fierce legal battle with her former employer, the Whittemore Peterson Institute for Neuro-Immune Disease, at the University of Nevada in Reno. The institute sponsored the XMRV research but has accused Dr. Mikovits, its erstwhile star scientist, of stealing laboratory notebooks and other materials—a charge she has denied. Public feuding between the institute and Dr. Mikovits ratcheted up as the hypothesis they jointly championed appeared to be falling apart. The institute filed a lawsuit against her earlier this month; she has also apparently been charged with “possession of stolen property,” according to a news update in Science. Last Friday, Dr. Mikovits was arrested in California as a “fugitive from justice” and spent the weekend in jail; she was released on bail after a hearing on Tuesday.)

Nevertheless, the heightened focus on CFS during the past couple of years has brought the illness greater attention from a larger group of scientists, including many infectious disease experts who had not previously given it much thought (e.g. the host of this blog, Columbia University virologist Vincent Racaniello). Experts now believe that one or a combination of viral or other infections, or perhaps other physiologic insults such as environmental toxins, can trigger an immune response that never shuts itself off; the immune response itself is likely the cause of many of the symptoms.

Dr. Racaniello said that when he used to question colleagues about chronic fatigue syndrome, they would argue that it was an imaginary illness. “Every time I asked someone about it, they would say it doesn’t exist, it isn’t a real disease, even as recently as the past year,” he said. “But once you start paying attention and reading papers, this looks like a chronic or hyper-immune activation. These patients have a lot of signs that their immune systems are firing almost constantly.” (Note: Dr. Racaniello is on the scientific advisory board of the CFIDS Association of America.)

According to this view, the revved up immune system is actually much less effective at controlling other infections, and studies have found associations between CFS and a grab-bag of pathogens, including members of the herpesvirus, parvovirus, and enterovirus families. Recent research from Norway has also lent support to the hypothesis that at least some people with CFS are suffering from a form of autoimmune disorder, perhaps triggered by one or multiple infections. Neurological impairments are also virtually always part of the complex; a study last year in the journal PLoS One found that people with CFS and a form of Lyme disease have patterns of proteins in their cerebrospinal fluid that clearly distinguish them from each other as well as from healthy controls.

In many cases, additional research has failed to confirm associations from prior studies. Yet there is a reasonable epidemiologic explanation for such divergent results: Most experts believe that there are likely many sub-groups or clusters of CFS patients, with a variety of infectious and possibly environmental exposures; studies that don’t account for such distinctions—and most haven’t–are much less likely to reach consistent results about causation or treatment. Moreover, different research groups have used different methods of identifying people with chronic fatigue syndrome, making it even harder to compare findings across studies—a situation that can encourage speculation that the roots of the illness lie in patients’ psyches.

“This ambiguity over definitions has made it difficult for researchers to pinpoint a biological cause,” wrote Leonard Jason, a professor of community psychology at DePaul University in Chicago and an expert in CFS, in an essay published this year in The Wall Street Journal. “When investigators compare very different samples, it is difficult, if not impossible, to replicate findings from one lab to another. And when consistent biological findings do not emerge, investigators might inappropriately conclude that CFS is only a psychiatric problem.”

In any event, the most promising research into the disease has been taking place not at the CDC or NIH but at academic medical centers; much of the new work is being funded by private donors who have family members with CFS. Researchers from Stanford, Harvard, University of Miami, Columbia, and other leading institutions are all engaged in innovative efforts focused on pathogenesis, diagnosis and treatment, and in particular on such issues as infectious triggers, biological markers, and medical therapies.

Dr. Derek Enlander, a longtime CFS clinician in New York, recently helped to launch an ME/CFS research and treatment center at Mt. Sinai Hospital; his highly regarded team hopes to explore genetic as well as other factors involved in the illness. The center was founded with the aid of a $1 million private donation, said Dr. Enlander, adding that such outside funding allows the group the freedom to pursue promising avenues of investigation. “I believe that an independent organization such as ours, which is not funded by the government or answerable to the government, can be the leader in new research,” said Dr. Enlander.

The Role of Case Definitions

Chronic fatigue syndrome is estimated to afflict about one million people in the U.S., although most remain undiagnosed. Some patients improve over time or have periods of better and worse health, but many remain disabled or even homebound for years. The symptoms include profound exhaustion, especially following minimal exertion, as well as disordered sleep, cognitive impairment, sore throat, and swollen lymph nodes, among others. It is one of a number of so-called “contested illnesses” that have emerged in recent decades to present thorny dilemmas for public policy and medical care; others include chronic Lyme disease, Gulf War syndrome, fibromyalgia, and multiple chemical sensitivity.

These conditions are characterized by shifting patterns of symptoms, a lack of agreed-upon biological markers and diagnostic tests, arguments over the interpretation of evidence, and competing claims of scientific authority. Patients presenting with these illnesses can bedevil doctors, who want to help but have few proven tools at their disposal. They might or might not be willing to try unorthodox strategies; some doctors clearly take advantage of patients who are desperate for relief. Such contested illnesses impact millions of people and their families, cost the U.S. billions in lost productivity, and consume a significant chunk of health care resources—and yet remain poorly understood. With so much at stake, they often emerge as societal and legal battlegrounds, with patients, clinicians, researchers, insurers, health officials and government bureaucrats all seeking to influence and control dialogue, debate and policy.

This conflict often plays out in struggles over a critical epidemiologic tool known as the “case definition”—a set of criteria for research or clinical use that ideally identifies all those who have a condition and screens out all those who don’t. Creating a case definition is easiest when a definitive laboratory test exists, as with HIV or hepatitis C. With an illness like CFS that is identified through symptoms, devising a completely accurate case definition is almost impossible; some people with the illness will always fall outside the parameters of the case definition, and some who have some other condition, or nothing at all, will be misdiagnosed—or will self-diagnose–as having CFS. Yet without a case definition that is as accurate as possible, researchers cannot achieve valid or reliable results.

“If you recognize something is happening, you need a case definition so you can count it,” Andrew Moss, an emeritus professor of epidemiology at the University of California, San Francisco, and an early AIDS investigator, told me for an article I wrote about case definitions earlier this year. “You need to know whether the numbers are going up or down, or whether treatment and prevention work. And if you have a bad case definition, then it’s very difficult to figure out what’s going on.”

Non-CDC researchers say the problem with the agency’s 2005 method for identifying CFS cases is that it mistakenly classifies people with primary depression as having chronic fatigue syndrome instead. Depression and CFS can resemble, overlap and interact with each other in multiple ways; patients with CFS may get very depressed about their situation, and depression often causes fatigue, as can many other ailments. So distinguishing chronic fatigue syndrome from primary depression—in other words, depression that preceded and perhaps caused the fatigue—is important but tricky, and requires nuanced instruments. In epidemiologic studies that conflate the two, treatments that are known to be effective for depression could appear to be effective for chronic fatigue syndrome, even if they might not be.

A case in point is a treatment called “graded exercise therapy,” a slow increase in exercise that has been promoted for CFS patients by the British psychiatric, medical, and insurance establishments; it is also highlighted as a treatment option on the CDC’s website and educational materials.

There is no dispute that exercise can be a very effective treatment for depression. But people with chronic fatigue syndrome generally suffer from a distinctive symptom known as “post-exertional malaise”—a disproportionate depletion of energy following minimal activity that is not a typical feature of depression. (However, the word ‘malaise,’ like the word ‘fatigue,’ is a complete misnomer; post-exertional malaise is much closer to a serious crash or relapse than a Victorian fainting spell.) An emerging field of research—much of it taking place at the University of Utah and University of the Pacific in Stockton, California–indicates that people with CFS suffer from problems with oxygen consumption, energy production and muscle recovery. So it’s not surprising that increasing activity levels could lead in some or many cases to a prolonged resurgence of their symptoms rather than the improvement predicted by proponents of graded exercise therapy.

Patients with CFS are very familiar with post-exertional malaise. Many report having recovered for a period of time, then pushing themselves too hard and suffering a devastating set-back, repeating the cycle multiple times before learning to adjust their pace. When Mary Schweitzer experiences post-exertional malaise, she said, she loses her formidable communications skills.

“I get close to incoherent,” she wrote in a recent e-mail. “I can’t make sense, and nobody can make much sense out of what I say. I am used to it now and try to make a joke out of it, but it’s sad.” As a result, she wrote, she has learned what people with CFS call ‘envelope theory,’ based on published work from Dr. Jason’s research group at DePaul University: how to harness their energy by recognizing their limits, and not pushing beyond them. That approach is essentially the antithesis of graded exercise therapy.

“You learn what will bring on a crash–sitting upright at a restaurant, for example–and you just don’t do it,” wrote Dr. Schweitzer. “You live in what we call your ‘envelope.’ Then if something special comes along like a birthday, you push the envelope, and if you get a push-back, you know you still have the same boundaries.”

Like Laura Hillenbrand, Mary Schweitzer is an author (although the book she wrote from her doctoral research at Johns Hopkins, Custom and Contract: Household, Government, and the Economy in Colonial Pennsylvania, has undoubtedly never reached Seabiscuit-y heights in Amazon’s rankings). She grew up in Richmond, Virginia; boogied in the mud at Woodstock; wooed her future husband, Bob, with home-cooked lasagna (he was the teaching assistant in an economics course she as an undergraduate at Duke); and was teaching, conducting research, and raising two kids when CFS whacked her life upside down.

Dr. Schweitzer said she could never have managed through the years without the support and devotion of her husband, a professor of finance and economics at the University of Delaware. But she has also improved significantly on intermittent treatment with Ampligen, a drug that appears to be effective for some people with CFS. The drug hasn’t been approved by the U.S. Food and Drug Administration, but Dr. Schweitzer currently receives it as part of an ongoing clinical trial. She travels twice a week from her home in Delaware to her doctor’s office in Manhattan for infusions of Ampligen; unlike in most clinical trials, she has to pay for the drug, which costs her $16,000 a year.

When off Ampligen, she has suffered major crashes; at one point several years ago, she tested positive for four herpesviruses—Epstein-Barr, cytomegalovirus, HHV-6A, and HHV-7—and Coxsackie B, an enterovirus. Whenever she can, she addresses public forums, in particular the twice-yearly meetings of the Chronic Fatigue Syndrome Advisory Committee, one of many committees created to offer guidance to the U.S. Department of Health and Human Services; she estimates that she has testified to date at thirty hearings, conferences or meetings. When she speaks, in a public forum or one-to-one, she is articulate, passionate, loud, tender, demanding, funny and fierce. In one of her many statements to the federal advisory committee, Dr. Schweitzer described one of her severe relapses.

“I lost the ability to walk normally and we had to bring the wheelchair back up from the basement,” she wrote. “I dropped things, and when I tried to load the dishwasher I crashed one glass against another…It made no difference that now I knew the names of the various symptoms–ataxia, expressive aphasia, short-term memory loss, central auditory processing dysfunction, etc. My brain had disappeared.”

A Bit of History

The conflict over the nature and definition of CFS–between the CDC and the patient community, as well as between the agency and other researchers–dates back to the initial investigations of an outbreak in Incline Village, Nevada, near Lake Tahoe, of a mysterious illness, possibly associated with Epstein-Barr virus. The outbreak was one of many reports in the mid-80s of what was already being called “chronic Epstein-Barr syndrome” or “chronic mononucleosis.” (Epstein-Barr virus causes most cases of mononucleosis).

In its 1988 paper on the illness, a CDC-led team of researchers cast doubt on the Epstein-Barr hypothesis and rechristened the phenomenon “chronic fatigue syndrome” to discourage unproven assumptions about viral origins. (Ironically, because CFS began as a suspected viral illness, the research program has remained housed in the agency’s viral section.) The paper proposed a complicated case definition requiring six months of unexplained fatigue, plus either six of eleven “symptom criteria” (mild fever, sore throat, painful lymph nodes, muscle weakness, muscle pain, prolonged fatigue post-exercise, headaches, joint pain, neuropsychological complaints, sleep disturbances, and sudden onset of the illness) and two of three “physical criteria” (fever, sore throat, and palpable or tender lymph nodes, documented by a physician twice, at least one month apart); or eight of the eleven symptom criteria, without the physical criteria.

In retrospect, for many patients the CDC’s first big blunder was in not calling the Tahoe illness myalgic encephalomyelitis in the first place. Benign myalgic encephalomyelitis has long been recognized by the World Health Organization as a synonym for “postviral fatigue syndrome,” which is listed as a neurological illness. The term was coined to refer to a similar flu-like outbreak at a major London hospital in the 1950s (although “benign” has since dropped out of common usage.) In practice, many patient and advocacy groups now combine the two terms as CFS/ME or ME/CFS, or use ME alone.

Dr. Reeves was not on hand for the original investigation, but joined the CDC in 1989 as chief of what was then called the Viral Exanthems and Herpesvirus Branch. Dr. Reeves received his B.A. in 1965 from the University of California, Berkeley, where his father was a renowned expert in mosquito-borne illnesses and served as dean of Berkeley’s School of Public Health; he studied medicine at University of California, San Francisco, earned a masters in epidemiology at the University of Washington, and worked at a major medical research center in Panama for a dozen years before joining the CDC in 1989.

A Harvard-led research team described the Tahoe outbreak in far more serious terms than the 1988 CDC report: the patients, they reported in 1992 in the Annals of Internal Medicine, had abnormal MRI brain scans, significant alterations in white blood cells counts and functioning, and signs of active infection with a recently discovered pathogen, HHV-6. The illness, they wrote, was likely a “chronic, immunologically mediated inflammatory process of the central nervous system.”

In a letter to the journal listing more than a dozen purported methodological flaws, the CDC—with Dr. Reeves as the lead author—dismissed the Harvard study and its findings in unusually blunt terms. “We conclude that the disease…described is not the chronic fatigue syndrome or any other clinical entity and that they showed no association with active HHV-6 replication,” wrote Dr. Reeves and his colleagues.

A pattern appeared to have been established. In a subsequent episode in the early 1990s, chronicled in detail in Osler’s Web, the CDC failed to confirm other researchers’ reports of a retroviral link to chronic fatigue syndrome. These and other contradictory results gave rise on both sides to claims and counter-claims and counter-counter-claims (etc.) of methodological flaws, unjustified assumptions, and other scientific sins of omission or commission.

In the early 1990s, a CDC-led team reviewed the complex 1988 case definition and published a revised and somewhat simplified version. According to these 1994 guidelines, a diagnosis of CFS required the presence of six months of disabling, medically unexplained fatigue, along with at least four of eight other symptoms: impaired memory or concentration, disordered or unrestful sleep, muscle pain, joint pain, headache, tender lymph nodes, sore throat, and post-exertional malaise. Although the definition relied on self-reported symptoms rather than biological tests or standardized instruments to measure levels of fatigue and disability, it soon became the most widely used set of criteria in both research and clinical settings.

The Financial Scandal

Two years after the CDC issued its 1994 case definition, Osler’s Web was published to strong reviews. The book documented how the CDC routinely diverted money slated for CFS research to other projects because of lack of concern about the illness. (The CDC did not officially comment on the book at the time, according to a CDC spokeswoman.) Two years later, Dr. Reeves leveled similar charges against his superiors, noting that the CDC lied to Congress about how it spent CFS funding; he received whistleblower protection.

In his statement, he reported that, for example, in 1996 the agency spent $1.2 million for laboratory equipment and supplies for measles and polio and charged it to the CFS account. In 1995, he reported, the agency charged the CFS program $2.6 million for funding spent on unrelated studies. He had, he stated “attempted to rectify this within CDC” before going public.

“I believe that CDC has intentionally misrepresented monies allocated to CFS research and I cannot ethically support this,” wrote Dr. Reeves in his public statement. “The misrepresentations involve systematically charging between $400,000 and $2 million incurred by unrelated activities to CFS between 1995-97 and reporting to DHHS [Department of Health and Human Services], Congress and patients that the monies were used for CFS research.”

A 1999 report from the inspector general of HHS found that of the $22.7 million the CDC charged to its CFS program between 1995 and 1998, less than half was clearly spent on the illness. The report noted: “CDC spent significant portions of CFS funds on the costs of other programs and activities unrelated to CFS and failed to adequately document the relevance of other costs charged to the CFS program…As a result of these inappropriate charges, CDC officials provided inaccurate information to Congress regarding the use of CFS funds.”

The inspector general’s report found that $8.8 million was spent on non-CFS projects and that the documentation on an additional $4.1 million was so poor that it was impossible to determine whether they were used to support CFS research or not. Even as the CDC shortchanged the CFS program, the report noted, it disregarded Congressional requests to support important research initiatives. As an example, the report noted that Congress had urged the CDC to expand its surveillance of CFS among adolescents and to hire a neuroendocrinologist “to enable expansion of its research efforts and pursue promising findings from other Federal agencies and the private sector.”

At the time of the inspector general’s report, however, the CDC had halted an ongoing adolescent study and had not hired an endocrinologist—even as allocated money wasn’t being spent. The report noted: “Internal correspondence… indicated that delays were forced due to a ‘lack of available funds.’ Yet, we found that large portions of budgeted CFS funds had been held in reserve by the Division Director during the year, and were not released until after the deadline for obligations had passed. Thus, while important enhancements were not being implemented, more than $850,000 of FY 1998 budgeted funds were never made available to the program.”

In the wake of the scandal, Dr. Reeves’ boss left his position; the agency agreed to reform its accounting practices and restore more than $12 million to the CFS program over the next several years. Although Dr. Reeves’ whistleblower status effectively solidified his position at the CDC, his statement didn’t answer all outstanding questions. Given the revelations from Osler’s Web in 1996, it seemed unlikely to many patients and advocates that key officials at the agency could have been unaware of accounting irregularities–especially since they apparently continued through 1998, according to the federal investigators.

A subsequent investigation in 2000 from the U.S. General Accounting Office (now called the Government Accountability Office) found that communication between the CDC and the NIH about CFS research programs and priorities was poor. The limited coordination, as well as the CDC misspending, had hampered progress in the search for answers to the illness, the investigators reported.

The financial scandal left many CFS advocates, patients and researchers with a lingering distrust toward the CDC. In the following years, however, some of the CDC’s work in chronic fatigue syndrome—funded by the millions restored to the budget–received praise.

In 2003, Dr. Reeves’ study of CFS in Wichita, Kansas, yielded a disease prevalence of 235 per 100,000 percent of the adult population, or about 400,000 overall in the U.S. That figure was below the generally accepted estimate of one million sufferers, derived from a community-based study in the Chicago area by Dr. Jason’s research group at DePaul University. Yet the new figure was accepted as far more accurate than the agency’s earlier estimates, from research in the 1990s, that less than 20,000 people had the illness; that research had been criticized for relying on doctors’ reports of patients with CFS, a far less effective epidemiologic method of assessing prevalence than community-based surveys. The Wichita research also provided a sense of the societal burden of CFS; the CDC team reported that the illness cost the economy $9.1 billion a year in lost productivity, and people with CFS lost an average $20,000 annually in earnings.

Also praised was the CDC’s partnership with Australian researchers on a study reporting that more than 10 percent of a cohort suffering from acute viral illnesses went on to develop CFS–one of the agency’s few successful efforts to document viral links. And in 2006, the CDC published—with great fanfare–a set of 14 studies in the journal Pharmacogenomics, which found significant variations in CFS patients of gene expression and activity related to how the body handles and adapts to physical and emotional challenges and stress.

Much of the research focused on genes associated with the hypothalamic-pituitary-adrenal axis, which regulates the body’s stress responses, among other functions. At a press conference introducing the studies, Dr. Reeves outlined his understanding of the illness: “The working hypothesis is that the HPA axis and the brain is a plastic organ which changes its actual physical architecture depending on stresses accumulated over the lifetime,” he explained. “So as people experience stress, and that can be childhood abuse, it can be childhood infections, it can be multiple injuries…to some extent the genetics determine how you are going to react to them, they determine how your allostatic load [a stress-related indicator] may accumulate, and more importantly, they actually determine your subsequent reaction to stress applied at a later time during the lifespan.”

Dr. Reeves himself declared the illness to be a matter of great public health concern and expressed empathy for patients. “People with CFS are as sick and as functionally impaired as someone with AIDS, with breast cancer, with chronic obstructive pulmonary disease,” he told me in 2007, when I wrote my first story about the disease for The New York Times.

Some advocates welcomed the genetics studies for providing evidence that the illness had a biological basis and was not a figment of patients’ imaginations. But a news article in Science about the Pharmacogenomics papers reported that other scientists had raised serious methodological questions about the CDC’s approach, with one prominent researcher calling the new findings “meaningless.” Others in the CFS community feared that the focus on stress and trauma as major factors left the door open for the CDC to focus on a wide range of psychologically and behaviorally oriented approaches in the search for both causes and treatments—and they note the recent personality disorder and childhood abuse studies as proof of their concerns.

The Rejected Empiric Criteria

Other CDC efforts, such as the multi-million-dollar public awareness campaign to brand the name “chronic fatigue syndrome,” dismayed much of the patient and advocacy community, given ongoing and fervent attempts to have the illness officially renamed ME. And in a highly controversial move, Dr. Reeves spearheaded in 2005 the creation of the new, purportedly more precise method of identifying patients; critics feared the approach would wreak havoc with epidemiologic studies by mixing a lot of people with depression but not CFS into samples of people all presumed to have chronic fatigue syndrome.

During the 2000s, researchers—including many clinicians who actually treated patients and understood how seriously ill they could be—had continued to be dissatisfied with the 1994 case definition, which they felt imprecisely described the condition. For one thing, the definition allowed for but did not require the presence of post-exertional malaise (reminder: read “relapse” or “crash,” rather than “malaise”). Yet it was increasingly apparent that post-exertional malaise, and not fatigue alone, was a cardinal symptom for many if not most patients, and one that clearly helped distinguish CFS from primary depression, as well as other chronic illnesses. The CDC definition also allowed for but did not require the presence of cognitive and neurological problems, although these appeared to afflict almost everyone with the condition.

Other research groups were using their own case definitions, making it hard to compare results. The “Oxford criteria” developed in Great Britain required only the presence of six months of disabling fatigue; that single-symptom criterion was criticized as so broad that it was likely to identify many people with primary depression rather than CFS. A more detailed 2003 case definition developed in Canada focused on post-exertional malaise as a cardinal symptom of what it called ME/CFS. Required symptoms also included disordered sleep, pain, and neurologic symptoms, as well as signs of dysfunction in the immune, endocrine and autonomic nervous systems.

Earlier this year, a team of top researchers—not surprisingly, without any participation from the CDC–published a new “international consensus” case definition, which adopted the name myalgic encephalomyelitis and abandoned chronic fatigue syndrome altogether. Using the Canadian definition as a jumping-off point, the new international definition also dropped the construct of “fatigue” in favor of requiring post-exertional malaise, which they renamed “post-exertional neuroimmune exhaustion.” Other required symptoms include neurological and energy production impairments.

In contrast, the 2005 effort by the CDC to “operationalize” the earlier 1994 case definition–by introducing standardized questionnaires and measurement scales to assess levels of fatigue and functional impairment—has found no support outside the CDC itself. In suggesting specific instruments and scales, Dr. Reeves and his research team proposed cut-off points to represent sufficient grounds for identifying CFS.

Yet when the CDC researchers applied these new “empiric” criteria, as they called them, to a population in Atlanta in 2007, they found a prevalence of 2.54 percent of the adult population. Extrapolated nationwide, that meant that four million people—in other words, ten times the CDC estimate from its Wichita research just four years earlier, and four times the widely accepted figure of about one million—had the illness. Dr. Reeves and his co-authors defended the new numbers, attributing the increased prevalence estimates to a broad sampling strategy and “application of more sensitive and specific measures of the CFS diagnostic parameters.”

Others outside the CDC dismissed the new numbers as absurdly inflated and argued that the empiric criteria, like the Oxford criteria but unlike the 2003 Canadian case definition, blurred and expanded rather than clarified the disease boundaries. While some advocates believed the increased estimates would focus more attention on the illness and should therefore be embraced, many others—including leading epidemiologists–believed that the expanded category could make it harder to isolate physiological correlates; that failure, in turn, would make it more likely that others would continue to perceive it to be largely a psychiatric illness.

One study from Dr. Jason’s research group at DePaul University, frequently cited by advocates, found that 38 percent of a group suffering from major depression but not chronic fatigue syndrome were misdiagnosed as having CFS using the new empiric case definition. The researchers reported that the scales, measurements and cut-off points indicated by the CDC group did not sufficiently distinguish between emotional and physiological sources of fatigue and disability; in other words, someone could be identified as having CFS under the new method solely because of fatigue or disability arising largely from psychological causes, such as depression.

“Given the CDC’s stature and respect in the scientific world, this new definition might be widely used by investigators and clinicians,” wrote Dr. Jason and his co-authors. “This might result in the erroneous inclusion of people with primary psychiatric conditions in CFS samples, with detrimental consequences for the interpretation of epidemiologic, etiologic, and treatment efficacy findings for people with CFS.” The authors also noted pointedly that the population prevalence for CFS calculated using the empiric definition was close to that for major depressive disorders.

Although the empiric case definition was published six years ago, it has not found any favor outside the CDC, raising questions about the comparability of CDC data derived from its use to results from other studies. Dr. Unger wrote in her e-mail response that she knew of no other researchers who had adopted the empiric criteria, although she noted that “others have started applying case definitions using instruments as tools, recognizing the improved ability to get consistent results.” Three major ongoing CDC studies have samples selected through use of the empiric criteria.

Dr. Unger appeared reluctant to whole-heartedly endorse the estimate, based on the empiric criteria, that 4 million people in the U.S. have CFS, but she did not back away from it either. “No single study or approach can be considered sufficient to determine the true population prevalence of an illness as complex as CFS,” she wrote. “Like all studies, the 2007 prevalence estimates of CFS based on the Georgia surveillance study are subject to the limitations of the study design. However, the Georgia study, along with those from other investigators, does demonstrate the public health importance of CFS and it is the CDC’s most recent study on the prevalence.”

Dr. Unger indicated that the agency “is in dialogue with other investigators about instruments and methods to best characterize and stratify CFS patients.” The agency is also launching studies with several investigators to enroll and characterize patients from seven clinical practices headed by leading CFS physicians to help clarify issues involving the case definition as well as the name.

“We are planning to collect standardized data on all the domains of illness included in the Canadian Consensus Criteria of CFS/ME, the 1994 CFS definition and the newly proposed International ME definition,” she wrote. “We anticipate that this data will assist researchers and clinicians in considering further refinements of the case definition.” With regards to the name of the illness, she wrote: “Opinions of advocates, clinicians and researchers remain divided about whether CFS and ME are the same or different entities. However, we are following the discussions with interest and would consider any consensus that is reached by patient groups and the scientific community going forward.”

The Website Conflict

Another conflict that has dogged the agency involves its CFS website. Advocates and patients have long complained that it conveys serious misinformation, in particular on aspects of diagnosis, treatment and management of the illness. For example, until this month the website included the following language: “No diagnostic tests for infectious agents, such as Epstein-Barr virus, enteroviruses, retroviruses, human herpesvirus 6, Candida albicans, and Mycoplasma incognita, are diagnostic for CFS and as such should not be used (except to identify an illness that would exclude a CFS diagnosis, such as mononucleosis). In addition, no immunologic tests, including cell profiling tests such as measurements of natural killer cell (NK) number or function, cytokine tests (e.g., interleukin-1, interleukin-6, or interferon), or cell marker tests (e.g., CD25 or CD16), have ever been shown to have value for diagnosing CFS. Other tests that must be regarded as experimental for making the diagnosis of CFS include the tilt table test for NMH, and imaging techniques such as MRI, PET-scan, or SPECT-scan.”

Advocates and patients appealed to the CDC many times over the years to remove the language. They acknowledged that these and other tests were not diagnostic for CFS but insisted that wasn’t the point; even though the tests couldn’t be used to confirm that a patient had CFS, they were important weapons for disease management. Experienced clinicians, like Dr. Enlander at Mt. Sinai and Dr. Nancy Klimas, a top researcher at the University of Miami, have long used tests such as these to identify CFS sub-groups and individualize treatment strategies, given their patients’ histories of immune dysregulation and viral infections. Yet clinicians report that they have received letters from insurance companies citing that paragraph in rejecting claims for tests they have ordered, in some cases as recently as last summer.

The agency finally removed that language this month, after an advisory group reviewed the website and requested a host of changes. “They [the reviewers] provided useful feedback in early October and CDC is incorporating this feedback into our ongoing efforts to improve the CFS website,” wrote Dr. Unger. Replacing the old language is a new passage that suggests that some of the same tests once disallowed for diagnosis of CFS can be useful for disease management—as advocates have been saying all along. Patient groups welcomed the change, but some advocates said it was minimal and long overdue, given that many insurance claims had been rejected unfairly in years past.

Another major complaint about the website has been the agency’s longstanding promotion of two treatments developed and championed in the United Kingdom: graded exercise therapy and cognitive behavior therapy. In the U.K, mental health professionals have dominated research into and treatment of chronic fatigue syndrome; they use the Oxford criteria, requiring only six months of unexplained fatigue. A major British study using this case definition and published earlier this year indicated some improvement with graded exercise therapy and cognitive behavior therapy. But U.S. experts on the illness, at least those outside the CDC’s immediate orbit, generally believe that the U.K. case definition—like the CDC’s empiric definition–is likely to define a cohort that includes a lot of people with depression, and not actual CFS, as their primary complaint.

To those convinced that CFS is a condition of psychogenic and not organic origin, it probably doesn’t matter if people with depression are mixed up in a study sample. In the framework of chronic fatigue syndrome endorsed by the British medical establishment, the prolonged fatigue and associated illness are largely considered to be caused by the patient’s inability or unwillingness to maintain an active lifestyle—an avoidance triggered by some form of stress, psychological issues or perhaps even an infectious illness. That avoidance of activity then leads to a physiological deconditioning that impacts multiple body systems and organs.

“It’s a psychological model,” said Dr. Jason of DePaul University, of the British view of CFS. “It’s an illness that might be caused by some kind of virus or trauma, but what’s maintaining it is that you have some sort of phobic avoidance of activity. The idea is your bone and muscle mass decrease, you become weak. So if you can get a person to slowly increase the amount of activity that they do, they will break this phobic avoidance.”

In the U.K. framework, graded exercise therapy is often paired with cognitive behavior therapy in the treatment protocol for CFS. Cognitive behavior therapy is a treatment modality with widespread application, and is likely to be useful to many people undergoing major stresses–whether from cancer, a back injury, an existential crisis, fear of sex, migraines, a bad divorce, or cognitive fatigue syndrome. However, the kind of cognitive behavior therapy prescribed in Great Britain to treat people with CFS—as Dr. Jason and other researchers have repeatedly noted–is largely geared toward convincing patients to overcome their avoidance phobia and increase activity levels; in other words, to encourage them to participate in something very much like graded exercise therapy.

But for people who experience post-exertional relapses of their symptoms, graded exercise therapy could be harmful, not helpful; in addition to the emerging research about post-exertional malaise, patient surveys in the U.K. have indicated a high degree of unhappiness and increased morbidity among those who have been through a course of graded exercise therapy. And, say critics, cognitive behavior therapy could also be harmful, if the goal is to convince patients to engage in graded exercise therapy or otherwise ramp up activity levels.

Dr. Unger wrote in her response that she was aware of patient concerns about including information on graded exercise therapy and cognitive behavior therapy on the website, and that the agency was reviewing those sections. The goal of the information, she wrote, was to let patients know about treatment options they could discuss with their health care providers. “Though these approaches may not work for everyone, the scientific literature shows that they provide some benefit to some patients,” she wrote.

However, Dr. Unger declined to comment specifically on the contested scientific literature from the U.K. that actually reported the modest benefits from these therapies, noting that “as a rule, CDC doesn’t comment on research not conducted by CDC.”

The View from the Chronic Fatigue Syndrome Advisory Committee

The growing dismay about Dr. Reeves’ leadership and the agency’s problematic CFS research program are evident in the minutes and testimony from the twice-yearly meetings in the late 2000s of the Chronic Fatigue Syndrome Advisory Committee of the Department of Health and Human Services. The mandate of the committee, with a rotating membership of clinicians, researchers, patients and advocates, is to offer guidance and recommendations to the department. In 2007, the committee requested financial records from the CDC’s CFS program. Dr. Jason, a member of the CFSAC, and Dr. Reeves, an ex officio member as the CDC’s representative, sparred publicly over access to the records.

By the time of the next CFSAC meeting, in October of 2008, Dr. Reeves had been replaced as the CDC’s ex officio member (although he retained his CDC position). Another CDC official at the meeting said he hoped the change would help “to leave behind past tensions to make a fresh start.”

At that meeting, however, Kim McCleary, the head of the CFIDS Association of America, testified that the CFS program, based on a review of the CDC financial documents that the committee had sought, suffered from “shameful scientific leadership, zero accountability, invisible outcomes and millions and millions of dollars stuck in suspended animation, if not wasted…Only the government contractors seem to be benefiting from millions spent for which there are no worthwhile outcomes for American taxpayers, or CFS patients.”

The largest chunk of the program’s funding, reported McCleary, went to a single private research organization, Abt Associates in Cambridge, Massachusetts, in sole-source or no-bid contracts for the epidemiologic research that was being widely criticized by other scientists. At least $2.7 million committed to Abt was “in limbo”–obligated to specific projects but remaining unspent—and work on other projects was proceeding slowly and at great cost, she testified. The financial mismanagement, testified McCleary, “has resulted in program management coming often to this committee and telling other investigators that no funds are available for new projects or collaborations.”

(The CFIDS Association of America had been criticized by some other advocates over the years for its previous close association with Dr. Reeves. The organization had provided essential public support for Dr. Reeves during the accounting scandal in the late 1990s; in the mid-to-late 2000s it implemented the agency’s controversial multi-million-dollar CFS public awareness campaign at a time when others were seeking to change the disease name. McCleary’s public rebuke of Dr. Reeves’ leadership, therefore, was viewed as a significant blow to the CFS program and found a welcome audience.)

McCleary’s report further shredded support for Dr. Reeves among committee members; some were researchers struggling with their own funding issues. The financial accounting appeared to confirm a frequently heard complaint about the CDC and Dr. Reeves—that they were not taking full advantage of opportunities to collaborate with outside scientists at academic research centers.

Christopher Snell, a professor of sports sciences at the University of the Pacific in Stockton, CA, and a committee member, stated, according to the minutes: “As somebody who works on a shoe string budget, when I start to look at some of these numbers, I was somewhat appalled… It just does not seem to be the best use of the funds. The thing that we asked for at a couple of previous meetings was for the CDC to consider more collaboration with outside entities. We meant people who work a lot cheaper. It would seem that there are people out there with great ideas who would love to work with the CDC for much less money.”

Dr. Klimas, also a committee member, noted that she had been collaborating with the CDC on a study comparing people with CFS and Gulf War illness, and that the agency had failed to finish its testing on samples, citing funding problems. She also unleashed another common charge: that the CDC was simply not interested in the role of pathogens. According to the minutes, “Dr. Klimas said that CDC has made it known that the agency has no intention of looking for infectious agents. She added that other research organizations are pursuing identification of pathogens and that CDC should be embarrassed not to be looking for them as well…despite the evidence, the CDC is still saying that viruses don’t matter in the illness even though people are already being treated for them. She said that the science is there to provide options way beyond the CDC’s recommended behavioral treatment and exercise.”

At its meeting in May 2009, the committee unanimously voted to recommend “progressive leadership” for the CFS program; although the recommendation, in an apparent nod to decorum, did not cite Dr. Reeves by name, the intent was clear. The request for a top personnel change—essentially a vote of no-confidence in the current leadership–was considered an aggressive move for this kind of federal advisory committee. At the same meeting, the International Association for CFS/ME, a leading scientific and research organization, endorsed the call for new leadership.

In October of 2009, Dr. Reeves committed what many in the CFS world regarded as a major public gaffe: an off-hand remark to a New York Times reporter (not this one) about the mouse retrovirus research that had just sparked a wave of excitement. In the interview, which occurred shortly after the publication of the Science paper reporting the link between XMRV and CFS, Dr. Reeves said his research team would look for the retrovirus but that they were unlikely to find anything. He told the Times: “If we validate it, great. My expectation is that we will not.”

For a scientist to predict his team’s outcomes in a contested field of research during a highly public and volatile debate is not the best way to demonstrate impartiality and open-mindedness (notwithstanding that the XMRV hypothesis appears not to have panned out). Even more so for someone like Dr. Reeves, who was already facing coordinated calls for his ouster from almost every corner.

At the CFSAC meeting later that month, the committee again approved a recommendation for new leadership and emphasized the urgency of the issue. According to the minutes: “CFSAC considers that recommendation important and would like to get some feedback, including whether or not the recommendation is being considered. This has become more important because of certain quotes that have been made in The New York Times concerning the retrovirus by the person in charge of the CDC program.”

The committee also formally rejected the CDC’s empiric case definition—the centerpiece of Dr. Reeves’ epidemiologic approach—and recommended support for “a national effort to arrive at a consensus definition of CFS that is accurate, standardized, and reflective of the true disease.”

Within months, Dr. Reeves was gone from his position, although no public explanation for the move was offered. For the most part, the elements of the CFS program that Dr. Reeves championed—the empiric criteria, the name of the illness, (most of) the disputed website information, etc.—remain in place under Dr. Unger.

Reaction to Dr. Unger’s efforts appears decidedly mixed so far. Yet some members of the research community express optimism about being able to develop, with Dr. Unger, the kind of cooperative framework that many felt was absent when Dr. Reeves ran the program. Dr. Fred Friedberg, president of the International Association for CFS/ME, said that Dr. Unger was “way more responsive” than Dr. Reeves, noting that she had attended the association’s annual conference this fall in Ottawa.

“We reached out to her and she has been very accommodating and engaged in conversation to talk about some joint efforts,” said Dr. Friedberg, a professor of psychology at Stony Brook University Medical Center. “It remains to be seen what goals she’s going to set up and what kind of studies she’s going to do exactly. So this is kind of a work in progress, but the level of cooperation is pretty good. For the first time in years, there’s an opening.”

Mr Tuller, forgive me for being so blunt: But I think I love you!
Thank you, thank you, thank you for this fantastic piece that I’m sure took you many hours to research. You covered every single important point and got it all completely right.

I have to say my faith in Dr. Unger is limited, so far I have only seen her defending the useless CDC definition. It would take a complete about-face to make up for decades of neglect and harm.

Thank you, too, Dr. Racaniello, for providing this opportunity to Mr. Tuller, it is very much appreciated.

Tom Kindlon

Hope to read this later. In the meantime, there is a petition against the empiric criteria at: http://www.ipetitions.com/petition/empirical_defn_and_CFS_research/index.html . It has over 2500 signatures. There is some extra information in the blog section.

anciendaze

One small correction: the CDC first investigated a non-resolving, flu-like illness in Punta Gorda Florida in 1956. Poskanzer and Henderson published an account in the NEJM in 1957. Henderson and Shelokov published a review of such outbreaks later. The diagnostic similarities were so pronounced that Henderson and Shelokov took part in discussions about naming the disease after those outbreaks described above took place. Both objected to the name CFS. Henderson has a remarkably good reputation in public health, due to his work on smallpox. Poskanzer taught neurology at Harvard Medical School. These are not people easily fooled by hysterical women or hypochondriacs.

Christopher Messina

Thank you David for increasing awareness about the core issues surrounding this disease.

Christopher Messina

Thank you David for increasing awareness about the core issues surrounding this disease.

Many, many thanks to Mr. Tuller for writing this piece and to Dr. Racaniello for publishing it on his widely-read blog.

I think it is EXTREMELY important for those in the science community to know this story, whether or not they have a specific interest in ME/CFS. There are, unfortunately, many occasions when science fails to live up to its own ideals of disinterested pursuit of the truth. Young scientists, or those without political experience, should be aware of the enormous role played by public agencies and institutions in determining which scientific problems get studied and which do not. This goes beyond “merely” providing or withholding resources for research. The actions and policy statements of public agencies play an enormous role in creating the “reality” in which “everybody knows” something – for instance, that a serious, painful, debilitating disease that can strike anyone without warning “doesn’t exist, it isn’t a real disease.”

ME/CFS patients often wonder why it is that their disease has been singled out for such special disdain and neglect. Certainly there is a social/cultural/economic component to this attitude: a disease of “fatigue” is a disease of unproductivity, so the stigma and contempt attached to it is not terribly surprising in our socioeconomic environment. Most people rightly fear the loss of their wage-earning ability, not just because it would destroy their livelihoods (especially because our social safety net for the disabled is horrendously inadequate), but because such a loss would profoundly damage their sense of self. Scapegoating and blaming those who fall victim to a disease like ME/CFS (and other “contested diseases”) can be seen a defense mechanism against that intolerable threat.

But the majority of individuals (including individual scientists and individual doctors) can only comfort themselves by brushing off the reality of a disease like ME/CFS when the larger institutional framework in which they operate allows them to do so. In the case of ME/CFS, US public health and scientific agencies have not just tolerated or supported such a view, but encouraged it. In recent years, it *seems* there has been a shift in public rhetoric by these agencies; but as long as this rhetoric is not supported by significant financial commitments, it will ring rather hollow.

This rhetorical shift is echoed in miniature in the consulting rooms of doctors. It seems to me that doctors are somewhat less likely than in the past to dismiss the ‘reality’ of the disease, at least to patients’ faces (although they still do so in inexcusably large numbers). However, I do not see much increased willingness on the part of doctors (and health insurance providers) to actually *behave* as though the disease is a serious one – for instance, by becoming informed about it, and exercising whatever due diligence is currently possible in properly treating it. Where is the accountability? Right back where we started – the standard of care cannot improve until public agencies take their leadership role seriously, and disseminate updated diagnosis and treatment guidelines that are science-based rather than assumption-based. The CDC’s “guidelines” on ME/CFS, to the extent that they have been based on unprovable negatives, can hardly be said to be science-based.

A thousand thanks again to David Tuller for this important article.

Anonymous

At the November 8th, 2011 HHS CFS Advisory Committee meeting, Dr. Nancy Lee told committee members they shouldn’t expect anything but virological studies from a research group in the Division of High Consequence Pathogens and Pathology.

As Dr. Nancy Klimas, who has been researching CFS since the early 90s and who even did a sabbatical with the CDC, replied – that that’s just it – they don’t do research on pathogens.

That pretty much says it all.

HR

Thank you David Tuller and Dr Vincent Racaniello for this article. Please keep up the good work!!

I’m a physician who treats people with ME/CFS. A patient referred me to this post. What a delight to find such a great piece of journalism – and such a great virology resource! I hope Mr. Tuller will continue to track developments in ME/CFS with his top-notch journalism skills.

Let’s close the curtains on the CDC/Oxford Follies and open them to a coherent and rigorous effort to solve this systems biology puzzle.

There is no mystery to Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). CFS/ME leads to HIV-Negative AIDS. It horrifies me on a regular basis that the medical establishment, politicians, and media have not gotten around to reporting the fact that HIV is not the cause of AIDS. While millions of ailing CFS/ME patients get belittled and neglected, very healthy HIV+ people are convinced to take a bunch of expensive, toxic medication. What a $ham. No mystery here; I am living proof that CFS/ME patients are the real AIDS patients. http://www.cfsstraighttalk.blogspot.com See how easy?

Jim in Smithfield, VA

If you want to support this web site and Prof Racaniello’s efforts to expand on it, please complete the survey at http://www.triplemojo.com/twiv/ that is still available.

Linden

Thank you so much for this.

Dan3ben

The viruses discovered in Lombardi et al and confirmed in Lo et al. have not been fully sequenced. What has been sequenced so far is ONLY polytropic, in both studies! Now when they are fully sequenced some will be a type of XMRV, but they are not prostate cancer XMRV and they are not the single strain VP62 explanation, a synthetic virus not found in nature that has been used by all the negative studies to optimise those assays. The same papers that all failed to clinically validate the assays used. Thus the negative papers have no impact on the findings of the two positive papers, as they looked for the wrong virus and did not prove the ability of the assays used. They should all be retracted and redone using clinically validated assays. Or they will only be incidental studies.

So it is wrong to say XMRV is over as there is no doubt HGRVs have begun.

Sleeper

Best article yet on why ME/CFS patients distrust the Center for Disease Control. The author has taken a very complex situation and nailed it. If only everyone in the ME/CFS community unstood the overall situation as well. Please stay with us Mr. Tuller as we need more to understand what’s been happening, and to move forward with the equally complex research misunderstandings. This is a truly fine piece of reporting!

Marian Smartt

Very simply, thank you!

This report is comprehensive, completely accurate and moving all at the same time. Finally someone is identifying PEM for what it really is. How correct that we do not have “Victorian fainting spells” but melt down with paralyzing fatigue and neurological symptoms!

Tom Kindlon

I’ve now read it – great work, David.

I will be recommending this to people to help them understand where I, and some other advocates, clinicians and researchers, are coming from. Indeed, I’ve already tweeted it, shared it on Facebook and Google+ and linked to it in the blog section of the petition against the empiric criteria: http://www.ipetitions.com/petition/empirical_defn_and_CFS_research/index.html

Kim McCleary

At this early hour on Thanksgiving, it seems fitting to express my gratitude to both host Vincent Racaniello and writer David Tuller for this fine history of the many challenges and complexities that persist in the study of CFS — and more importantly — the lives of those affected by this disease. Thank you for sharing your research and insights, David, and for sharing your faithful audience, Vincent.

ixchelkali

A big thank you to David Tuller for writing this and to Vincent Racaniello for posting it on your website. For a long time I’ve wished that someone would write up a summary of this convoluted history in a way that would be accessible to scientists who might be entering into ME/CFS research. I think it’s hard for someone coming into the field to understand some of the dynamics of the patient community without knowing the back-story. I think it’s hard for most people to credit the politics of ME/CFS research unless they’ve lived through it. The CDC enjoys such a good reputation in many areas, that without knowing the context, some of the patients’ suspicions might seem strange or nutty.

David Tuller has done a fine job here of summarizing the highlights. Really, HBO could do a series about this story.

To me, the issue of a case definition that yields well-defined patient cohorts is of paramount importance. It has been a serious flaw in much of the existing research and I believe it’s the major reason we don’t have widely accepted biomarkers. You mentioned that patients feel the CDC has dismissed much of the evidence that ME/CFS is an organic illness. The thing that floors me is that they haven’t even followed up on their own research, such as the Pharmacogenetics studies. Over and over, these papers conclude with “more research is needed,” and yet the CDC doesn’t conduct the needed follow-up studies.

Again, thanks to both of you.

ixchelkali

Just a quick question. You said “Cognitive behavior therapy is a treatment modality with widespread application, and is likely to be useful to many people undergoing major stresses–whether from cancer, a back injury, an existential crisis, fear of sex, migraines, a bad divorce, or cognitive fatigue syndrome.” Is there really a cognitive fatigue syndrome, or was a lovely Freudean slip?

Dowzer

I’ve been sick for over 30 years, and generally stay away from reading about the politics of this illness because it sends me back into despair. However, I thank you for researching and writing this piece, and I thank the publisher for putting it out there. Please stay on the case!!

Kdurkin

I’m too tired right now from my CFS ailments, but I was sent to this article from a very good Facebook blog. I didn’t have the energy to read the entire piece, but I am so elated to see this.
You have done so much research and interviewed several people with CFS or medical people, and this has turned out to be an excellent contribution on the CFS conundrum.
This and the news of Dr. Enlander’s new center at Mount Sinai, and the research being done around the country, albeit it with mostly private donations, has buoyed my spirits.
I will come back and read this in its entirety when I have energy, and will print it out and give it to medical people, friends and family members.
And, by the way “fatigue” describes how we feel as poorly as “malaise” describe the post-exertional
suffering. I’d rather “bone-deep exhaustion” and “post-exertional collapse.” Unless one has this disease or lives with someone who does, it is perhaps hard to fathom exhaustion so bad that one can’t take a shower, wash one’s hair, do the laundry or make a meal. Or walk to to the corner to mail a letter. Or go to the close-by grocery store. Or “collapse” so bad that one can barely make it from one room to another in one’s residence.
But in the scheme of the advance of understanding the mysteries of CFS, this article has the merit of an entire book!

Kdurkin

I’m too tired right now from my CFS ailments, but I was sent to this article from a very good Facebook blog. I didn’t have the energy to read the entire piece, but I am so elated to see this.
You have done so much research and interviewed several people with CFS or medical people, and this has turned out to be an excellent contribution on the CFS conundrum.
This and the news of Dr. Enlander’s new center at Mount Sinai, and the research being done around the country, albeit it with mostly private donations, has buoyed my spirits.
I will come back and read this in its entirety when I have energy, and will print it out and give it to medical people, friends and family members.
And, by the way “fatigue” describes how we feel as poorly as “malaise” describe the post-exertional
suffering. I’d rather “bone-deep exhaustion” and “post-exertional collapse.” Unless one has this disease or lives with someone who does, it is perhaps hard to fathom exhaustion so bad that one can’t take a shower, wash one’s hair, do the laundry or make a meal. Or walk to to the corner to mail a letter. Or go to the close-by grocery store. Or “collapse” so bad that one can barely make it from one room to another in one’s residence.
But in the scheme of the advance of understanding the mysteries of CFS, this article has the merit of an entire book!

Julia Hugo Rachel

Thank You for this article on ME/CFS and a bit of the historical and political history which has played a dominany role in forming the political anfd medical climate for these diseases. My son nearly died of CFS, I have been a patient of 30 plus years with this disease. When my son became ill, I realized that this disease was not only becoming more prevelant in society, but that it was escalating as far as loss to the national economy, loss to the work and tax base and was being proven to be linked with other escalating diseases such as Autism/GWI/Lyme Disease/Epilepsy and MS,; plus certain types of cancers. No longer was ME/CFS in the “Yuppie Flu” Ballpark; we are now looking at serious diseases that are intertwined involving immunology, infectious disease, virology, epidemiology, cardiology, reproductive disorders, neurochemistry, genetics and more. i contacted a law firm to talke political action on behalf of these linked and associated diseases. the first thing the Lawyers asked me was to find out why the CDC has turned their heads to these diseases. what do they have to gain? Amongst that question, were 6-10 other questions which took our team months to unravel. although we are not convcerned with the ‘whys” of how these diseases have reached a pandemic stage, we are concerned primarily with cutting down prevention numbers and fuelingb research in order to treat those afflicted and suffering. I’ve heard many theories and disserations on historical accounts of the CDC’s stance and procedures on handling these diseases. yet, I’ not heard a single evidenced based reason explaining their behavior. This hot topic issue has crossed the libe from oversight hearings, committees, meetings with constituents and has now reached the phase of Professional National Political Action. The 50,000 foot aerial view of this sitaution clearly shows that major change is on the way. The day to to day drama, is just that. Benign diversion. Its time to get poltical. Its’ time for action and change.
Julia Hugo Rachel
very lucky Girl on Valcyte Blog

Anonymous

Thank you, David Tuller, this is a great overview! May I add that the real tragedy caused by the lack of a decent case definition and treatment understanding is that patients necessarily go undiagnosed for at least six months, with some never getting a diagnosis. The problem with this is that the longer one tries to ignore the illness and push through the symptoms, the further into the illness one gets; recovery becomes harder with each successive crash.
The status quo on ME/cfs means that there are more of us, and we are more sick. The urgency of the situation cannot be overestimated. A few weeks ago I got a phone call from a friend of my brother, a professional woman who feared she was going mad, as the doctor told her there was nothing wrong with her, yet when she tried to carry on as usual she became so ill that she was forced to her bed in pain and distress. She had been ill for only a month and obviously had Classic Post Exertional Meltdown, or Post exertional malaise as it’s known. The cardinal symptom of ME. She also fit the International Consensus Criteria for ME in all the other respects. After ascertaining this, I suggested she clear her diary, and rest rest rest. Eat right, and add a few simple nutritional supplements. I heard from her a couple of weeks later, she was feeling much better, following my suggestions. I hope she gives it enough time to really work, but so far so good… So different to my own experience, left to lurch around in the dark until it was too late. Despite there are multiple punctate lesions and areas of low perfusion on my MRI scan, the neurologist told me I did “not have ME, as there was no such thing – errr… it’s very rare.”She is the third of four new sufferers that have been referred to me by my family. The pattern with the others is unknown, they have not come back to me. I hope no news is good news here. My strong feeling is that if action is taken in the early stages of this illness, recovery is possible, and it is not expensive. If we are left floundering, with a Dx of depression, as many of us are (and I laughed at the doc when he said that to me) then we end up chronically sick, some of us for many decades.Just saying… anecdotal I know… can this be tested in a study?… because it’s a more valid hypothesis than the one most medics work on at present… though that might be changing. Once again, thanks, David, for illuminating a very sorry tale.

Anonymous

Thank you, David Tuller, this is a great overview! May I add that the real tragedy caused by the lack of a decent case definition and treatment understanding is that patients necessarily go undiagnosed for at least six months, with some never getting a diagnosis. The problem with this is that the longer one tries to ignore the illness and push through the symptoms, the further into the illness one gets; recovery becomes harder with each successive crash.
The status quo on ME/cfs means that there are more of us, and we are more sick. The urgency of the situation cannot be overestimated. A few weeks ago I got a phone call from a friend of my brother, a professional woman who feared she was going mad, as the doctor told her there was nothing wrong with her, yet when she tried to carry on as usual she became so ill that she was forced to her bed in pain and distress. She had been ill for only a month and obviously had Classic Post Exertional Meltdown, or Post exertional malaise as it’s known. The cardinal symptom of ME. She also fit the International Consensus Criteria for ME in all the other respects. After ascertaining this, I suggested she clear her diary, and rest rest rest. Eat right, and add a few simple nutritional supplements. I heard from her a couple of weeks later, she was feeling much better, following my suggestions. I hope she gives it enough time to really work, but so far so good… So different to my own experience, left to lurch around in the dark until it was too late. Despite there are multiple punctate lesions and areas of low perfusion on my MRI scan, the neurologist told me I did “not have ME, as there was no such thing – errr… it’s very rare.” The above example is the third of four new sufferers that have been referred to me by my family this year. The pattern with the others is unknown, they have not come back to me. I hope no news is good news here. My strong feeling is that if action is taken in the early stages of this illness, recovery is possible, and it is not expensive. If we are left floundering, with a Dx of depression, as many of us are (and I laughed at the doc when he said that to me) then we end up chronically sick, some of us for many decades. Just saying… anecdotal I know… can this be tested in a study?… because it’s a more valid hypothesis than the one most medics work on at present… though that might be changing. Once again, thanks, David, for illuminating a very sorry tale.

rivka

fantastic piece of research and writing. next should be a similarly researched article on xmrv, because many of us still think we have a human gamma retrovirus, even if it is not specifically called xmrv.

Annwhit52

Thank you David for your excellent article about the challenges that those who are touched by this disease faces on a daily basis. The good news includes the active interest by individuals at the highest levels of the NIH and the many re-energized physician researchers including Dr Frank Malderelli of the NIAID. Pathogen studies and immune system research continues to provide very real clues to this disease. I remain encouraged by the many PhD researchers who are now committed to discovery that can lead to effective treatments. In addition the recovery of WPI’s priceless research materials this past week assures the continuity of our exhaustive search for much needed answers.

Caroline Fribance

Many thanks for this excellent article. I agree with virtually all the comments already made. Something else to be thankful for on Thanksgiving Day. Wow!

Anonymous

It is rare that someone with ME/CFS feels respected by either a journalist or a doctor. But this wonderful, comprehensive article carefully lays out, brick by brick, the tale of the CDC vs. ME/CFS. (I chose the word “versus” carefully.) It’s not a nice story.

In my own little world, this piece will help my friends understand the stress I feel after suffering M.E. for 20 years while the CDC’s inertia destroyed the credibility of my pain. And let’s hope it also reaches doctors. A few weeks ago I told my doctor that the CDC’s influence on ME/CFS was like acid rain falling on a forest. I will give her this piece, and she may believe me. For a very long time, the CDC has shaped the attitude of the public, journalists, and our doctors toward ME/CFS with careless, inaccurate information. As a result, it has helped to decimate the dignity, relationships, and careers of ME/CFS patients. Its intractability has pushed many of us into the depths of poverty because (as Tuller mentions) insurers, like the public, regard the CDC as the soul of medical enlightenment. Unfortunately, in our case, its neglect has been tantamount to abuse. And this legacy keeps on growing. That’s why it’s imperative that the CDC’s ME/CFS position change–not later, or soon, but right away. Now. And in some way it must make the change known. I hate this cliche, but the agency must be “nimble.” So far, Elizabeth Unger has been anything but nimble. Yes, being cautious and careful is often the better part of valor. And listening is not just good but new. Unfortunately, the decades-long injustice inflicted on ME/CFS patients demands that Unger translate whatever she’s learning into intelligent, transformative action. Can she do it? Well, there’s a dim hope. …. I live in a gray state of very dim hope. For many people with ME/CFS, hope is dim or non-existent re the CDC. We have learned by brutal, sad experience.Back to the bright side–thank you, David Tuller, for terrific analysis and reporting.

Sarissass

Thank you Mr. Tuller for writing this article and Dr. Rancanciello for posting it. This is a thoughtful and well-researched piece. As a scientist with ME/CFS, I am glad that the history of the CDC in regards to ME/CFS was explored and exposed. I have a lot of respect for the CDC and at one point had considered working there but the way that the CDC has treated ME/CFS is not only scientifically but morally wrong.

Medical history is full of examples of illnesses that were regarded as psychological before the science advanced far enough to show that the illness was in fact entirely biologically based. Yet we obviously have not learned from this history. The story of ME/CFS is important not just for ME/CFS sufferers, families, clinicians, and researchers but for everyone could be affected by any poorly understood illness in the future.

Taniaaust1

Thank you greatly Mr Tuller for being a journalist who obviously puts in the hard work and really investigates the story.

Winterkoning

Dear Mr Tuller and Professor Racaniello,

Thank you.

It feels like the world is slowly opening its eyes.
And the truth is like a virus, it can spread like mad.
Ours just had a really long incubation period.

Winterkoning

Dear Mr Tuller and Professor Racaniello,

Thank you.

It feels like the world is slowly opening its eyes.
And the truth is like a virus, it can spread like mad.
Ours just had a really long incubation period.

The CDC’s ME/CFS ‘neurosis’ paper not only did not include another chronic illness control group such as multiple sclerosis, but actually cites a 2003 paper which did use the same questionnaires with ME/CFS vs. multiple sclerosis patients. The CDC however almost completely misrepresents the cited paper’s findings, as multiple sclerosis patients had basically the same scores as were reported in the ME/CFS patients. Since multiple sclerosis is an accepted organic disease, the authors of that paper were forced to take the time to critically assess their results and not just publish bull*(&*. The authors of the 2003 paper reported that- “we expected CFS patients to score higher than the MS patients on the Neuroticism scale of the NEO-FFI. Consistent with two other studies comparing personality of CFS and MS patients [20,29], we did not find any difference between the two diagnostic groups. Moreover, consistent with the findings that levels of neuroticism increase after the onset of a chronic illness [19], both diagnostic groups scored higher than the general population on neuroticism.”

This is how the CDC referred to the above paper- “In general, a positive association between neuroticism and fatigue has been found [14] , with CFS patients showing higher levels compared to healthy controls [15] and the general population [16]. These studies clearly highlight the important role of neuroticism in CFS.”

This issue has also been dealt with in other disease groups such as RA, again however once you actually take the time to give appropriate consideration to the results you end up with a much more simple solution, namely that subjective tests on personality are not appropriate to be given to patients suffering from chronic disease. I personally would like to see a study on ‘Personality disorders in acute influenza patients’, in which the fact that patients are sick is totally ignored, similar to other studies on ‘personality disorders’ in chronic disease groups. Such as study should bring some attention and common sense to the issue.

“The Minnesota Multiphasic Personality Inventory (MMPI) scales for Hypochondriasis, Depression, and Hysteria were studied in patients with rheumatoid arthritis (RA). The RA patients showed elevated scores on these scales, and these results are similar to those reported in each of 6 published studies. The elevated MMPI scale scores can be explained largely by 5 “disease-related” MMPI statements which met 2 criteria: (a) they were among 11 of the 117 MMPI statements that two-thirds of rheumatologists predicted would be RA-associated; and (b) RA patients and normal subjects differed significantly in their responses to these statements. The responses of RA patients and normal subjects to most other statements in the MMPI Hypochondriasis, Depression, and Hysteria scales were quite similar. In RA patients, responses to “disease-related” statements were correlated with results of measures of disease activity, which indicates that responses to these MMPI items reflect the severity, as well as the presence, of RA. These findings suggest that new criteria are needed for validation of the MMPI as a clinical tool for the recognition of hypochondriasis, depression, and hysteria in a patient who has RA.”http://onlinelibrary.wiley.com/doi/10.1002/art.1780291206/abstract

Sarah L

Wow, thank you for this clear, concise article, telling a story I have been living through. Put so clearly, I almost understand why there are FEWER doctors in the large Chicago metro area who will treat me seriously, once they know my main diagnosis, than there were when I contracted this disease.

It seems we are left at the door of the CDC, an agency that seems a world unto itself, and is never publicly wrong. How will that agency make itself useful, or at least get out of the way?

I am ever more grateful for all the privately funded research happening in the US and other countries. But I know that a good privately funded study needs to make the leap to the big time with federal funding, and some respect from that almost faceless federal medical bureaucracy.

I just spent Thanksgiving day with a huge family gathering. I will pay for this adventure, far beyond my envelope. In the perverse way of this disease, I need sleep desperately now. But I cannot sleep and will not, for hours, until my body undoes what it did for me to survive today (on just 3 hours sleep before the event began). This article is balm to my soul. That much concentrated, independent and accurate journalism explaining the advocacy and the recalcitrance in the time I have been ill and then fully disabled.

My training was not in a medical field, and I cannot predict the final outcome of retrovirus studies. Yet I think that XMRV did catch the notice of the virologists and retrovirologists. I am glad that this vigorous community of researchers and clinicians is awake to this disease now, and thus thank both Vincent Rancaniello, owner of the blog, and David Tuller, writer of these words.

“Non-CDC researchers say the problem with the agency’s 2005 method for
identifying CFS cases is that it mistakenly classifies people with
primary depression as having chronic fatigue syndrome instead.
Depression and CFS can resemble, overlap and interact with each other in
multiple ways; patients with CFS may get very depressed about their
situation, and depression often causes fatigue, as can many other
ailments.”

There is, of course, a third confounder here – or rather, a potentially enormous group of other confounders, besides depression, barely hinted at in the phrase “many other ailments.”

Since fatigue, in and of itself, is an extremely common symptom of many illlnesses — common or rare — any definition of “CFS” that primarily focuses upon persistent “medically unexplained” fatigue, and is not sufficiently specific about other, more characteristic symptoms of ME/CFS, is bound to become a very large tent indeed. This is the inherent problem with a ‘diagnosis of exclusion’ – it assumes that every other possibility *has* been excluded.

If we are lucky (and most of us are not even that lucky) we will be tested for most of the obvious knucklehead stuff that could cause our fatigue — diabetes, thyroid disorders, leukemia, etc. — before we get tossed in the diagnostic wastebasket of “CFS.” However, we also know that diagnostic screening is never perfect, and plenty of diseases get missed – even the common ones; certainly the rare ones. Symptoms that are “medically unexplained” at any given moment often represent wrong diagnoses, missed diagnoses, or delayed diagnoses.

It seems to me that failing to be rigorous about case definitions of ME/CFS does a terrible disservice, not just to those who in all likelihood have “true” ME/CFS, but to patients with other ailments who may fall through the medical cracks if a diagnosis of “CFS” is pinned on them in error. This is a particular danger since virtually everyone who receives a diagnosis of “CFS” experiences a sharp fall-off in medical attentiveness after diagnosis. Patients and doctors alike are simply forced to accept so many floridly horrific symptoms as a daily norm that it becomes very difficult to discern when something “else” is wrong.

Condy Eckerle

This is a fair and accurate account of what has happened in part during the past quarter century. I sincerely thank David Tuller for his reportage of the story, he has gone farther than anyone else I have read in his grasp of the facts of this story. Also thanks to Vincent Racaniello for putting it up on his blog, even as the CFS world erupts in yet another scandal, this one surrounding a retrovirus and a researcher of retroviruses.
But “CFS” is a unique scandal in medical history, one that dwarfs the Tuskeegee Experiement in size and scope, and there is a parallel history of incompetence, obstinance, prejudice and outright fraud that guided the “CFS Program” in NIAID under Stephen Straus and Anthony Faucci who were instrumental and equally culpable as the CDC for creating the stigma that has dogged this illness as a modern form of hysteria,even as they collected money to study the illness as an infectious disease. They were supposed to research infectious agents which were turning up regularly in the CFS patient population, everything from EBV, HHV6, CMV, Borellia, Chlamydia Pneumoniae, yet FAILED to do follow up on most of this data and actively discouraged Drs. who were finding these pathogens in their CFS patients. They also ignored the immunological abnormalities that are known to be rife in the patient population, PUBLISHED DATA, though it should have been their unique role as an Immunology institute to follow up on this data. The same thing was going on at NIAID as was going on at the CDC. The CFS money was a slush fund, though we were never able to get the GAO to audit the program, there was enough evidence to say that something was amiss with the way money was spent. The fact that the lead investigator, Stephen Straus, never published any of his research into CFS should be a red flag Look at all the data clinicians published on shoestring budgets compared to Straus during the same time frame. What was he actually doing for all of those years?. He got away with it. “CFS” is a dark and scandalous chapter in medical history that needs to be compared to the Tuskeegee experiment in order to understand the willful nature of the actions of the public health service AGAINST a hapless class of medical patients, whom they clearly victimized. While I hope that things are changing at the CDC and NIH, it would help their credibility if they admitted to the scope of their role in this outrageous scandal, and cleaned house of all persons who were ever remotely involved in the “CFS Programs” that are emblematic of this abuse.

Heartfelt thanks for reporting on the
CFS case-definition subterfuge and on the breakthrough ME
International Consensus Criteria. Reading between the lines, I don’t
suppose The New York Times will be telling this sordid tale
anytime soon. More’s the shame!

I can not express how thankful I am that a reporter of your caliber is ‘on the case.’ Hillary Johnson is a true hero for her authoritative reporting on CDC and NIH’s decades-long war on ME science and patients. I love Osler’s Web and have always wished there were a shorter version of the story, both as a book and as a series of media articles so that everyone could know the horrible abuse CDC and NIH has subjected us too. Thank you for realizing this dream of mine. I am assuming NYTimes did not wish to print this story and, if so, that is a huge shame. Please do try to get this published there if you can.

May I suggest you also write pieces on NIH and the situation in the UK, which is even worse than here due to Simon Wessely and his co-conspirators’ hold on the health system and media there.

You have done a huge service to an extremely disabled and oppressed population. Again, Thank you!

Justin Reilly, esq.

Debo

Great work Mr. Tuller and much appreciation to your host, Prof. Racaniello. The piece brings to mind two questions I think important:
1. Do the people who have so callously botched ME/CFS research at the CDC have no caring or love for their fellow human beings?
2.Do they feel no sense of duty towards the American citizens who are paying their very decent salaries, health care benefits far better than the majority of Americans can hope for, and substantial pensions?

GuruJ

I suppose we should thank the CDC for being so stridently opposed to the use of ME since it means that better research agencies can now use ME with a minimum of confusion…

What’s the best online resource for the international researchers who are focusing on the “Canadian ME” definition? Sounds like the best bet is to ignore the CDC and to wait for non-US researchers to make a breakthrough!

Joan

I was willing to go along with this article until it referred to “a form of Lyme disease.” There is only one kind of Lyme disease, and it’s not the “chronic Lyme” that quacks and their victims insist exists. If this article is predicated on the kind of gullibility that would accept the existence of “chronic Lyme” uncritically, I don’t think any of it is worth consideration.

Kdurkin

Again, this is a great article and a real contribution to the study of CFS, and will help to push forward understanding and validation of it, research and funding.
One thing: I do not think that the CFS scandal in the CDC is quite like the Tuskegee experiment when 600 African-American people who had syphilis were not told they had the disease. The study lasted from 1932-1972. Even after penicillin was found to effectively treat the disease in the 1940s, the drug was not given to them. So many needlessly suffered and died. That was racist in addition to being cruel, uncaring and insensitive. It was really criminal medical neglect and a lot worse.
Also, on Lyme disease, there is chronic disease. A friend has become incapacitated and homebound, unable to even use her computer from Lyme disease, which went undetected for several years. She now has opportunistic infections, to boot. I believe Dr. Natelson’s study in N.J. found abnormal proteins in the spinal fluid of people with CFS and Lyme disease, and knowing more about this should help in studying both diseases.
A lot of research is going on now. Wish the NIH were funding and doing more. Thanks to the private donors and the Norwegian doctors and others. Dr. Enlander may come up with a lot of concrete information, which could help us all.

I think that CDC and NIH’s malfeasance and nonfeasance re ME is as bad as or worse than in the Tuskegee experiment. The immorality and harm done to each patient was worse in Tuskegee, but CDC has victimized the 17 million pwME worldwide as opposed to 600 in Tuskegee. The point is they are criminals abusing the disabled and must be stopped.